AB0472 INFECTIOUS PROFILE IN PATIENTS WITH ANCA-ASSOCIATED VASCULITIS: RETROSPECTIVE ANALYSIS IN A REFERRAL CENTRE

Background:The antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) are rare multisystem autoimmune diseases of unknown cause, characterised by inflammatory cell infiltration causing necrosis of blood vessels. The treatment of AAV requires prolonged immunosuppressive therapy. Infections remain a major cause of morbidity and mortality.Objectives:The aim of our study was to investigate the prevalence and characteristics of infection, and analyse the factors associated with infection in patients with AAV from Northern of Spain.Methods:Retrospective, descriptive study of patients with AAV followed in a specific Systemic Autoimmune Diseases and Thrombosis Unit from January 2000 to December 2019. Demographic, laboratory, microbiology, treatment and clinical data were collected from the medical records. AAV was diagnosed according to the definitions of the Chapel Hill nomenclature and designated as granulomatosis with polyangiitis (GPA), eosinophilic granulomatosis with polyangiitis (EGPA), microscopic polyangiitis (MPA) or pauci-immune necrotizing and/or crescentic glomerulonephritis without systemic vasculitis (renal-limited vasculitis, RLV). Disease activity of AAV was evaluated by Birmingham Vasculitis Activity score (BVAS). The infection episode was considered on the basis of clinical, laboratory, microbiology, radiology information, and response to therapy. Different episodes of infection in one patient were independently reflected. Data were analysed using SPSS 25.0Results:Thirty-six patients of which 20 (55.6%) were males. Median follow-up was 42 months. The mean age at the diagnosis was 61.14 ± 17.49 years and mean BVAS was 18.81 ± 5.96. 15 patients were diagnosed of GPA, 13 of MPA, 5 of EGPA and 3 of RLV. 72.2% MPO, 11.1% PR3. Lung involvement occurred in 75% of patients, upper airways was detected in 41.7%, skin involvement in 16.7%, Nervous system affectation occurred in 33.3%. 30 patients (83.3%) had renal affectation with a mean of 1.93± 1.66 gr/dl of Proteinuria and 2.9±2.17mg/dl of creatinine. We detected hypocomplementemia in 27.8% of patients (C3 in 19.4% and C4 in 16.7%). Regarding induction treatments, all patients received corticoids at high doses, 21 (58.3%) Cyclophosphamide, 3 (20%) Rituximab and 2 (13.3%) patients, Azathioprine. When we analyse infections, we detected 15 patients (41.66%) who presented any infection after the diagnosis of AAV, with a total of 71 episodes of infection. The most frequent were bacterial infections (29 episodes), specifically gram negative pathogens. The most frequent location was the respiratory (56.3%) followed by urinary (22.5%) and Skin (8.5%). Also opportunistic infections were described: 3 patients with Aspergillus fumigatus and one patient with Cryptococcus neoformans. 41 of these episodes needed hospitalisation with a median stay of 11 days. 6 episodes warranted intensive care unit (ICU) admission. Infection related mortality was 2.82%. We made latent tuberculosis screening and Pneumocystis prophylaxis in all our patients. No cases of Tuberculosis or Pneumocystis were recorded. Factors associated with increased risk of hospitalisation with statistical signification in univariated study were MPA, Hypocomplementemia and increased BVAS. But in the logistical regression study, only the value of the BVAS maintained statistical significance. The only factor associated with elevated risk of ICU admission was IgG deficit in the multivariate analysis. Neither immunosuppressive therapy nor age was associated with increased risk of infection in our study.Conclusion:More than 50% of the episodes of infection needed hospitalisation in patients with AAV. Risk factors for hospitalisation and ICU admission were BVAS and IgG deficit respectively. Bacterial infections were the most frequent but fungal infections were the most severe.Disclosure of Interests:None declared

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POS1230 OUTCOME FOLLOWING COVID-19 INFECTION IN ANTI-NEUTROPHIL CYTOPLASMIC ANTIBODY (ANCA)-ASSOCIATED VASCULITIS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.3020 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 898.2-898

Author(s):

A. Antovic ◽

B. Lövström ◽

A. Hugelius ◽

O. Borjesson ◽

A. Bruchfeld ◽

...

Keyword(s):

Maintenance Therapy ◽

Immunosuppressive Therapy ◽

Granulomatosis With Polyangiitis ◽

Renal Involvement ◽

Data Retrieval ◽

Induction Treatment ◽

High Dose ◽

Eosinophilic Granulomatosis With Polyangiitis ◽

Upper Airways ◽

Anca Associated Vasculitis

Background:Patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) require immunosuppressive therapy for disease control and reduction of disease relapse and may be at risk for complications during Sars-CoV-2 (COVID-19) infection.Objectives:To analyze the consequences of COVID-19 in a large cohort of AAV patients regarding occurrence, need of hospitalization, treatment at the intensive care units (ICU), or death.Methods:Data were retrieved from March 2020 to mid-January 2021 from medical records from the AAV cohort (n=233). Patients diagnosed with granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA) or eosinophilic granulomatosis with polyangiitis (EGPA) were included. Data included age, gender, diagnosis, ongoing immunosuppressive medication at onset of COVID-19 or at last follow-up in non-COVID individuals. Renal involvement (ever) and estimated glomerular filtration rate (eGFR) were included. COVID-19 was confirmed either by a positive PCR test in the upper airways or by serology. Severe COVID-19 was defined as need of non-invasive ventilation, ICU care, and/or death.Results:The cohort comprised of 172 patients with GPA, 50 with MPA and 11 with EGPA. There were 121 females (52%). During the study period, 20 patients (8.6%) were diagnosed with COVID-19. The median age at data retrieval in all patients was 68 years (21-93), in the COVID-19 group 63 (29-93) and 68.5 (21-90) years in the non-COVID patients.Fourty-three patients in all (18%) were hospitalized during the study period of which 11 (4.7%) due to COVID-19 infection. In all, 8 deaths occurred of which 3 were related to COVID-19.At data retrieval, 110 (47%) patients were on prednisolone treatment, 10/20 (50%) in the COVID-19 group and 100 (47%) in the non-COVID-19 group (p=0.5), with significantly higher doses in COVID-19 patients (p<0.001). In patients hospitalized with COVID-19, 6/11 (54.5%) were on prednisolone, median dose 5 mg/day (0-50). In the total group 112 (48%) were on disease modifying anti-rheumatic drugs (DMARD) and 64 (27.5%) on rituximab as maintenance therapy. Eight patients were on induction treatment with either cyclophosphamide or rituximab.Of the 20 COVID-19 cases, 8 had severe COVID-19. Of these, 2 were inactive without immunosuppressive treatment, 4 had stable disease with prednisolone (5-7.5 mg/day) in combination with DMARDs, and 2 were active treated with high dose prednisolone (25-50 mg/day) in combination with cyclophosphamide and rituximab (n=1) or rituximab (n=1).A higher proportion of patients had active AAV (p=0.03) in the severe COVID-19 then in the non-COVID group (10/213 patients).In the group with the severe COVID-19, 1/8 (12%) patient had rituximab as maintenance therapy, compared to 61/213 (28.6%) in the group of non-COVID-19 patients (p=0.5).Renal involvement (ever) was present in 144 patients (62%), in 6 patients (30%) with COVID- 19, from which 5 (62%) were in the group of severe COVID-19 patients. Median eGFR did not differ between severe COVID-19 and remaining patients with renal involvement independently of COVID-19 infection.Conclusion:We found a high rate of severe COVID-19 infection in our cohort of AAV patients which indicates risk for serious complications, especially in patients with active disease and intense immunosuppressive therapy. Maintenance therapy with rituximab did not seem to increase the risk for severe COVID-19. The findings stress the need for continued shielding and early vaccination in AAV patients.Disclosure of Interests:None declared

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Factors associated with COVID-19 related hospitalisation, critical care admission and mortality using linked primary and secondary care data

10.1101/2021.01.19.20241844 ◽

2021 ◽

Author(s):

Lisa Cummins ◽

Irene Ebyarimpa ◽

Nathan Cheetham ◽

Victoria Tzortziou Brown ◽

Katie Brennan ◽

...

Keyword(s):

Risk Factors ◽

Learning Disabilities ◽

Secondary Care ◽

Multivariate Logistic Regression Analysis ◽

Additional Patient ◽

Factors Associated ◽

Icu Admission ◽

Risk Of Death ◽

North East ◽

Increased Risk

AbstractBackgroundTo identify risk factors associated with increased risk of hospitalisation, intensive care unit (ICU) admission and mortality in inner North East London (NEL) during the first UK COVID-19 wave.MethodsMultivariate logistic regression analysis on linked primary and secondary care data from people aged 16 or older with confirmed COVID-19 infection between 01/02/2020-30/06/2020 determined odds ratios (OR), 95% confidence intervals (CI) and p-values for the association between demographic, deprivation and clinical factors with COVID-19 hospitalisation, ICU admission and mortality.ResultsOver the study period 1,781 people were diagnosed with COVID-19, of whom 1,195 (67%) were hospitalised, 152 (9%) admitted to ICU and 400 (23%) died. Results confirm previously identified risk factors: being male, or of Black or Asian ethnicity, or aged over 50. Obesity, type 2 diabetes and chronic kidney disease (CKD) increased the risk of hospitalisation. Obesity increased the risk of being admitted to ICU. Underlying CKD, stroke and dementia in-creased the risk of death. Having learning disabilities was strongly associated with increased risk of death (OR=4.75, 95%CI=(1.91,11.84), p=0.001). Having three or four co-morbidities increased the risk of hospitalisation (OR=2.34,95%CI=(1.55,3.54),p<0.001;OR=2.40, 95%CI=(1.55,3.73), p<0.001 respectively) and death (OR=2.61, 95%CI=(1.59,4.28), p<0.001;OR=4.07, 95% CI= (2.48,6.69), p<0.001 respectively).ConclusionsWe confirm that age, sex, ethnicity, obesity, CKD and diabetes are important determinants of risk of COVID-19 hospitalisation or death. For the first time, we also identify people with learning disabilities and multi-morbidity as additional patient cohorts that need to be actively protected during COVID-19 waves.

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ANCA-associated vasculitis in a 14 years-old patient: a clinical case

Kuban Scientific Medical Bulletin ◽

10.25207/1608-6228-2020-27-5-184-194 ◽

2020 ◽

Vol 27 (5) ◽

pp. 184-194

Author(s):

A. V. Burlutskaya ◽

N. V. Savelyeva ◽

N. S. Тaran

Keyword(s):

Respiratory Failure ◽

Immunosuppressive Therapy ◽

Clinical Case ◽

Granulomatosis With Polyangiitis ◽

Systemic Vasculitis ◽

Pulse Therapy ◽

Eosinophilic Granulomatosis With Polyangiitis ◽

Anca Associated Vasculitis ◽

Nasal Bleeding ◽

Diagnostic Research

Background. ANCA-associated systemic vasculitis is a rare childhood disease. Antineutrophil cytoplasmic autoantibodies (ANCA)-related vasculitises include microscopic polyangiitis, granulomatosis with polyangiitis and eosinophilic granulomatosis with polyangiitis. Their rarity often leads to a late diagnosis, rapid disability and high mortality in patients due to aggressive respiratory, pulmonary lesion and renal failure.Clinical Case Description. The patient suffered from a recurrent bronchoobstructive syndrome with signs of respiratory failure, obscure origin fever and chronic rhinitis with nasal bleeding for 6 months. The patient was diagnosed with obstructive bronchitis (putative bronchial asthma debut), received antibacterial therapy and inhalation bronchodilators without stable improvement during the entire period. Skin haemorrhages and arthralgia stimulated diagnostic research to establish ANCA-associated systemic vasculitis (presence of proteinase 3-specifi c ANCAs in titre 1/80). CT lung scanning revealed frosted glass foci of reduced pulmonary pneumatisation and signs of bilateral bronchoobstruction. Immunosuppressive therapy with glucocorticosteroids (methylprednisolone pulse therapy No. 3, 1000 mg intravenously on alternate days, subsequent per os administration of 1 mg/kg/day) and cyclophosphamide (500 mg intravenously once per 28 days) was prescribed. This led to the positive dynamics with eliminated fever and skin haemorrhages, as well as essentially reduced signs of respiratory failure.Conclusion. Diagnosis of systemic vasculitis is often complicated and long-term due to commonly non-specifi c debut symptoms of autoimmune disorders. In the described case, the fi rst 6 months of illness displayed intoxication and bronchoobstruction with signs of respiratory failure. Haemorrhagic rashes, arthralgias and the presence of ANCAs are proxy to vasculitis. Standard immunosuppressive therapy for ANCA-associated vasculitis improved the patient’s condition.

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Anabolic Androgen (Oxymetholone) Improved Failure Free Survival in Childhood Severe Aplastic Anemia Responding to Immunosuppressive Therapy.

Blood ◽

10.1182/blood.v108.11.982.982 ◽

2006 ◽

Vol 108 (11) ◽

pp. 982-982

Author(s):

Dae-Chul Jeong ◽

Hui Sung Hwang ◽

Bin Cho ◽

Nak Gyun Chung ◽

Pil Sang Chang ◽

...

Keyword(s):

Multivariate Analysis ◽

Aplastic Anemia ◽

Immunosuppressive Therapy ◽

Response To Therapy ◽

Severe Aplastic Anemia ◽

Not Given ◽

First Line ◽

Free Survival ◽

Factors Associated ◽

Significant Difference

Abstract Immunosuppressive therapy (IST) has been extensively used as first line treatment in children with severe aplastic anemia (SAA), who do not have a suitable donor for hematopoietic stem cell transplantation (HSCT). Several studies have reported that androgens may enhance the response to IST. We retrospectively investigated the effects of androgen on survival. The patient population consisted of 112 children with diagnosis with SAA at St. Mary’s Hospital between 1991 and 2004. All patients received horse type anti-lymphocyte (ALG) or rabbit type anti-thymocyte globulin (ATG), and methylprednisolone, cyclosporin A without G-CSF. Forty-seven children began oral administration of oxymetholone (OMT, 2mg/kg/day) at post-IST 4 weeks for 3 months. We assessed response at post-IST 4 weeks, 6 months on the basis of Camitta’s criteria. Treatment failure was defined as transfusion dependency, death, clonal evolution, and progression to HSCT. We analyzed failure free survival (FFS) and overall survival (OS) in childhood SAA treated with IST. There were no differences in patient characteristics but children treated with ALG received more OMT than those treated with ATG (P < 0.01). The response rate at post-IST 6 months was 57.1%, 24.1% showing a complete response (CR) and 33.0% a partial response (PR). A high CR rate was identified in those treated with OMT administration (P = 0.04). Factors associated with response to therapy were type of anti-globulin utilized, response at post-IST 4 weeks, and the administration of OMT (P < 0.01). The relapse rate was 40.6%, and was noted to be higher in those given ALG. The OS and FFS in this study was 77.6 ± 4.3% and 54.5 ± 5.1% respectively at 8 year. Factors associated with FFS were response at post-IST 6 months (P < 0.01, RR: 2.155, 1.246 ~ 3.728) and the administration of OMT (P = 0.04, RR: 1.830, 1.026 ~ 3.265) in multivariate analysis, although type of anti-globulin was also included in univariate analysis. The FFS was higher in those treated with OMT (74.3 ± 6.4%) than those who were not given OMT (33.5 ± 7.3%) at 8 year. With regards to the type of response, the FFS was higher in those administered OMT (80.0 ± 10.3%) than those not given OMT (26.4 ± 14.9%) (P = 0.02, RR: 2.273, 1.1624 ~ 12.064) amongst patients who showed PR, although there was no significant difference in FFS amongst patients who showed CR with OMT (94.7 ± 9.0%) or without OMT (83.3 ± 15.2%) at 8 year (P = 0.76). The factor associated with OS was response at post-IST 6 months (P = 0.013, RR: 3.30, 1.28 ~ 8.52) in multivariate analysis, although severity at diagnosis was also included in univariate analysis.Our data revealed that OMT improved FFS in childhood SAA responding to IST, especially in those with PR. In this retrospective study, we concluded that the addition of short term OMT to IST as first line therapy significantly improved CR rate and FFS in childhood SAA patients without a suitable HLA-matched donor.

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Subarachnoid Hemorrhage and Prostatic Involvement in Granulomatosis with Polyangiitis – An Atypical Presentation

Journal of Clinical Rheumatology and Immunology ◽

10.1142/s2661341719720015 ◽

2019 ◽

Vol 19 (01) ◽

pp. 34-39

Author(s):

Raymond Bak Hei Chu ◽

Priscilla Ching Han Wong ◽

Joey Ka Ming Wai ◽

Florence Hiu Yi Yap

Keyword(s):

Subarachnoid Hemorrhage ◽

Vertebral Artery ◽

Immunosuppressive Therapy ◽

Acute Urinary Retention ◽

Granulomatosis With Polyangiitis ◽

Rare Complication ◽

Artery Aneurysm ◽

Atypical Presentation ◽

Anca Associated Vasculitis ◽

First Case

Granulomatosis with Polyangiitis (GPA) is a form of Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis. We report a case of a 56-year-old man with GPA who first presented with acute urinary retention, and then developed pulmonarycavitating lesions and subarachnoid hemorrhage (SAH). The SAH was due to a ruptured right vertebral artery aneurysm, whichwas subsequently embolized. The patient initially had a good response to immunosuppressive therapy but later succumbed due to fulminant sepsis. SAH is a rare complication of GPA and usually not associated with a detectable aneurysm. Our patient is thesecond case in the literature where an aneurysm had been detected on angiography and the first case where examination of the culprit aneurysm revealed features of vasculitis.

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Factors Associated With Fatality Due to Avian Influenza A(H7N9) Infection in China

Clinical Infectious Diseases ◽

10.1093/cid/ciz779 ◽

2019 ◽

Vol 71 (1) ◽

pp. 128-132 ◽

Cited By ~ 1

Author(s):

Shufa Zheng ◽

Qianda Zou ◽

Xiaochen Wang ◽

Jiaqi Bao ◽

Fei Yu ◽

...

Keyword(s):

Risk Factors ◽

Avian Influenza ◽

Influenza A ◽

Bacterial Infections ◽

Neuraminidase Inhibitor ◽

Inhibitor Therapy ◽

H7n9 Virus ◽

Factors Associated ◽

Risk Of Death ◽

Increased Risk

Abstract Background The high case fatality rate of influenza A(H7N9)-infected patients has been a major clinical concern. Methods To identify the common causes of death due to H7N9 as well as identify risk factors associated with the high inpatient mortality, we retrospectively collected clinical treatment information from 350 hospitalized human cases of H7N9 virus in mainland China during 2013–2017, of which 109 (31.1%) had died, and systematically analyzed the patients’ clinical characteristics and risk factors for death. Results The median age at time of infection was 57 years, whereas the median age at time of death was 61 years, significantly older than those who survived. In contrast to previous studies, we found nosocomial infections comprising Acinetobacter baumannii and Klebsiella most commonly associated with secondary bacterial infections, which was likely due to the high utilization of supportive therapies, including mechanical ventilation (52.6%), extracorporeal membrane oxygenation (14%), continuous renal replacement therapy (19.1%), and artificial liver therapy (9.7%). Age, time from illness onset to antiviral therapy initiation, and secondary bacterial infection were independent risk factors for death. Age >65 years, secondary bacterial infections, and initiation of neuraminidase-inhibitor therapy after 5 days from symptom onset were associated with increased risk of death. Conclusions Death among H7N9 virus–infected patients occurred rapidly after hospital admission, especially among older patients, followed by severe hypoxemia and multisystem organ failure. Our results show that early neuraminidase-inhibitor therapy and reduction of secondary bacterial infections can help reduce mortality. Characterization of 350 hospitalized avian influenza A(H7N9)-infected patients in China shows that age >65 years, secondary bacterial infections, and initiation of neuraminidase-inhibitor therapy after 5 days from symptom onset were associated with increased risk of death.

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Factors associated with COVID-19 severity and mortality among Hispanic patients living on the USA–Mexico border

Journal of Investigative Medicine ◽

10.1136/jim-2020-001667 ◽

2021 ◽

pp. jim-2020-001667

Author(s):

Jorge Cervantes ◽

Amit Sureen ◽

Gian Galura ◽

Christopher Dodoo ◽

Alok Kumar Dwivedi ◽

...

Keyword(s):

Multivariable Analysis ◽

Ethnic Disparities ◽

Factors Associated ◽

Icu Admission ◽

Risk Of Death ◽

Imaging Characteristics ◽

Increased Risk ◽

Hispanic Patients ◽

The Usa ◽

Mexico Border

COVID-19 has ravaged the medical, social, and financial landscape across the world, and the USA–Mexico border is no exception. Although some risk factors for COVID-19 severity and mortality have already been identified in various ethnic cohorts, there remains a paucity of data among Hispanics, particularly those living on borders. Ethnic disparities in COVID-19 outcomes in Hispanic and black populations have been reported. We sought to identify the clinical presentation, treatment, laboratory, and imaging characteristics of 82 Hispanic patients in a county hospital and describe the factors associated with rates of hospitalization, intensive care unit (ICU) admission, and mortality. The most common comorbidities were hypertension (48.8%) and diabetes mellitus (DM) (39%), both found to be associated with hospitalization and mortality, while only DM was associated with increased rate of ICU admission. Multivariable analysis showed that individuals with fever, low oxygen saturation (SpO2), nasal congestion, shortness of breath, and DM had an increased risk of hospitalization. Individuals with fever, decreased levels of SpO2, and advanced age were found to be associated with an increased risk of death. The most common cause of death was respiratory failure (28.9%), followed by shock (17.8%) and acute kidney injury (15.6%). Our findings are critical to developing strategies and identifying at-risk individuals in a Hispanic population living on borders. Research aiming to identify key evidence‐based prognostic factors in our patient population will help inform our healthcare providers so that best interventions can be implemented to improve the outcomes of patients with COVID-19.

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Association of the systemic host immune response with acute hyperglycemia in mechanically ventilated septic patients

PLoS ONE ◽

10.1371/journal.pone.0248853 ◽

2021 ◽

Vol 16 (3) ◽

pp. e0248853

Author(s):

Nauman Farooq ◽

Byron Chuan ◽

Hussain Mahmud ◽

Samar R. El Khoudary ◽

Seyed Mehdi Nouraie ◽

...

Keyword(s):

Immune Response ◽

Blood Glucose ◽

Critically Ill ◽

Bacterial Infections ◽

Pearson Correlation ◽

Glycemic Variability ◽

Host Immune Response ◽

Pentraxin 3 ◽

Icu Admission ◽

Increased Risk

Hyperglycemia during sepsis is associated with increased organ dysfunction and higher mortality. The role of the host immune response in development of hyperglycemia during sepsis remains unclear. We performed a retrospective analysis of critically ill adult septic patients requiring mechanical ventilation (n = 153) to study the relationship between hyperglycemia and ten markers of the host injury and immune response measured on the first day of ICU admission (baseline). We determined associations between each biomarker and: (1) glucose, insulin, and c-peptide levels at the time of biomarker collection by Pearson correlation; (2) average glucose and glycemic variability in the first two days of ICU admission by linear regression; and (3) occurrence of hyperglycemia (blood glucose>180mg/dL) by logistic regression. Results were adjusted for age, pre-existing diabetes mellitus, severity of illness, and total insulin and glucocorticoid dose. Baseline plasma levels of ST2 and procalcitonin were positively correlated with average blood glucose and glycemic variability in the first two days of ICU admission in unadjusted and adjusted analyses. Additionally, higher baseline ST2, IL-1ra, procalcitonin, and pentraxin-3 levels were associated with increased risk of hyperglycemia. Our results suggest associations between the host immune response and hyperglycemia in critically ill septic patients particularly implicating the interleukin-1 axis (IL-1ra), the interleukin-33 axis (ST2), and the host response to bacterial infections (procalcitonin, pentraxin-3).

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Prevalence and Risk Factors for Major Infections in Patients with Antineutrophil Cytoplasmic Antibody–associated Vasculitis: Influence on the Disease Outcome

The Journal of Rheumatology ◽

10.3899/jrheum.190065 ◽

2019 ◽

Vol 47 (3) ◽

pp. 407-414 ◽

Cited By ~ 5

Author(s):

Eloi Garcia-Vives ◽

Alfons Segarra-Medrano ◽

Ferran Martinez-Valle ◽

Irene Agraz ◽

Roser Solans-Laque

Keyword(s):

Bacterial Infections ◽

Granulomatosis With Polyangiitis ◽

Opportunistic Infections ◽

Disease Onset ◽

Antineutrophil Cytoplasmic Antibody ◽

First Year ◽

Laboratory Findings ◽

Anca Associated Vasculitis ◽

Tertiary Center ◽

Tract Infections

Objective.To analyze the role that infections play on the antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) outcome.Methods.A retrospective study of adult patients with AAV diagnosed in a tertiary center. Clinical features, laboratory findings, treatment, relapses, major infections, and outcome were evaluated.Results.Included were 132 patients [51 microscopic polyangiitis (MPA), 52 granulomatosis with polyangiitis (GPA), 29 eosinophilic GPA (EGPA)] with a mean followup of 140 (96–228) months. ANCA were positive in 85% of cases. A total of 300 major infections, mainly bacterial (85%), occurred in 60% patients during the followup. Lower respiratory tract (64%) and urinary tract infections (11%) were the most frequent, followed by bacteremia (10%). A total of 7.3% opportunistic infections were observed, most due to systemic mycosis. Up to 46% of all opportunistic infections took place in the first year of diagnosis, and 55% of them under cyclophosphamide (CYC) treatment. Bacterial infections were associated with Birmingham Vasculitis Activity Score (version 3) > 15 at the disease onset, a total cumulative CYC dose > 8.65 g, dialysis, and development of leukopenia during the followup. Leukopenia was the only factor independently related to opportunistic infections. Forty-four patients died, half from infection. Patients who had major infections had an increased mortality from any cause.Conclusion.Our results confirm that major infections are the main cause of death in patients with AAV.

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Novel ways to monitor immunosuppression in pediatric kidney transplant recipients—underlying concepts and emerging data

Molecular and Cellular Pediatrics ◽

10.1186/s40348-021-00118-8 ◽

2021 ◽

Vol 8 (1) ◽

Author(s):

Thurid Ahlenstiel-Grunow ◽

Lars Pape

Keyword(s):

Kidney Transplantation ◽

Immunosuppressive Therapy ◽

Bacterial Infections ◽

Immunosuppressive Drugs ◽

Immune Defense ◽

Therapeutic Interventions ◽

Kidney Transplant Recipients ◽

Post Transplant ◽

Pediatric Kidney Transplantation ◽

Increased Risk

AbstractAfter pediatric kidney transplantation, immunosuppressive therapy is given to avoid acute and chronic rejections. However, the immunosuppression causes an increased risk of severe viral complications and bacterial infections and is associated with serious side effects. It is therefore crucial to achieve the optimal individual balance between over- and under-immunosuppression and thereby avoid unnecessary exposure to immunosuppressive drugs. In routine use, steering of immunosuppressants is performed primarily by monitoring of trough levels that mirror pharmacokinetics (although not, however, pharmacodynamics). Other diagnostic and prognostic markers to assess the individual intensity of immunosuppression are missing. Potential methods to determine immune function and grade of immunosuppression, such as analysis of the torque teno virus (TTV) load, QuantiFERON Monitor®, and ImmuKnow® as well as virus-specific T cells (Tvis), are currently being evaluated. In some studies TTV load, QuantiFERON Monitor® and ImmuKnow® were associated with the risk for post-transplant rejections and infections, but randomized controlled trials after pediatric kidney transplantation are not available. Post-transplant monitoring of Tvis levels seem to be promising because Tvis control virus replication and have been shown to correlate with virus-specific as well as general cellular immune defense, which represents the individual’s susceptibility to infections. Additional Tvis-monitoring provides an innovative opportunity to personalize the antiviral management and the dosing of the immunosuppressive therapy after pediatric kidney transplantation to avoid unnecessary therapeutic interventions and identify over-immunosuppression.

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